Sodium hyaluronate, collagen gels and chondroitin sulfate solutions have been used in the anterior chamber to protect the corneal endothelium from intraocular lens trauma and to maintain anterior chamber depth. Additionally, hyaluronate and collagen gels have been used as vitreous replacements. None of these materials has proven to be ideal in such applications.
Chondroitin sulfate solutions do not exhibit pseudoplastic behavior, i.e., the viscosity is relatively constant at all shear rates. Accordingly, chondroitin sulfate solutions do not exhibit the same degree of anterior chamber support as pseudoplastic fluids such as those prepared using sodium hyaluronate. Furthermore, since the viscosity of the chondroitin sulfate solutions does not decrease at increasing shear rates (as do pseudoplastic materials) extremely high pressures are needed to apply or irrigate chondroitin sulfate solutions through a syringe (MacRae et al., "The Effects of Sodium Hyaluronate, Chondroitin Sulfate, and Methyl Cellulose on the Corneal Endothelium and Intraocular Pressure," American Journal of Ophthalmology, 95:332-341 (1983)). Additionally, commercially available chondroitin sulfate solutions (20 to 50 percent solutions) have osmolarities in excess of 500 mOs.sub.m. Such high osmolarities are detrimental to the corneal endothelium. Lastly, as reported by MacRae et al. in the American Journal of Ophthalmology, supra, 20 percent chondroitin sulfate may cause a sharp increase in intraocular pressure in the first one to four hours after intracameral injection and, therefore, anterior chamber washout is indicated.
Stenzel et al. ("Collagen Gels: Design for a Vitreous Replacement", Science 164: 1282-1283 (1969)), Dunn et al. ("Collagen-Derived Membrane: Corneal Implantation", Science, 157: 1329-1330 (1967)) and Rubin et al. ("Collagen as a Vehicle for Drug Delivery", J. Clinical Pharmacology, Aug-Sept., Pages 309-312 (1973)) have described the use of stabilized collagen membranes and gels to serve as drug delivery devices, vitreous replacement gels and cornea transplants. Introduction of crosslinks was accomplished by heat, ultraviolet radiation or glutaraldehyde reaction.
U.S. Pat. No. 4,409,332 discloses membranes and gels composed of complexes of reconstituted collagen with alkaline phosphatase, crosslinked with glutaraldehyde, UV radiation or gamma radiation. These complexes are said to be useful as vitreous replacements for ophthalmologic therapy.
U.S. Pat. No. 4,164,559 describes a chemically-modified collagen membrane which is useful as a carrier for ophthalmic medication. The collagen compounds disclosed are single collagen units which have been acylated or esterified.
Collagen as an anterior chamber replacement is described by Kawakami ("Operation for Aftercataract with the Injection of Collagen Gel into the Anterior Chamber", Excerpta Medica International Congress Series, Vol. 2 (450), pages 1432-1434 (1975)). This investigation describes the injection of ultraviolet crosslinked collagen gel into the anterior chamber prior to extraction of the aftercataract.
The collagen gels described hereinabove have greater viscosities and thus afford more protection and support to eye tissues than does chondroitin sulfate. However, known collagen gels are not pseudoplastic and fragment into small pieces when injected through a syringe. Additionally, collagen gels are generally hazy materials and have been known to cause inflammatory reactions in the anterior chamber and the vitreous (Advances in Vitreous Surgery, pages 601-623, Irvine and O'Malley, 1976).
Furthermore, collagen gels injected into the anterior chamber may cause an elevation of intraocular pressure (Kawakami, E., "Operation for Aftercataract with the Injection of Collagen Gel into the Anterior Chamber", supra).
Neither the chondroitin sulfate solutions nor the collagen gels used in ophthalmic surgery are viscoelastic materials. Viscoelastic ophthalmic materials are preferred for several reasons. During surgery, viscoelastic materials protect cell and tissue surfaces from mechanical trauma; create space by separating two adjacent but not adherent tissue surfaces, or by breaking normal or pathological tissue adhesions; maintain space allowing for safe surgical manipulations or by permitting the insertion of implants without dislocating or touching sensitive tissues; contain hemorrhages; and also act as a "soft instrument" or "surgical tool" to move, manipulate or relocate tissues.
After surgery, viscosurgical materials may be used to retain space for a desired period of time, prevent or minimize postsurgical inflammation and localize bleeding, restrain fibrin coagulation, hold back inflammatory cells, and lubricate tissue surfaces which move relative to each other and thereby prevent adhesion formation.
U.S. Pat. No. 4,141,973 discloses the use of highly-pure hyaluronic acid for both vitreous and aqueous replacement. This material is colorless, transparent, nontoxic and viscoelastic. However, it too has a number of drawbacks. The most abundant natural source of hyaluronic acid is rooster combs. Due to the low yield from this source coupled with the relatively complicated process involved in extracting and isolating this compound, hyaluronic acid is an expensive product. Secondly, while hyaluronic acid appears to be efficacious in reducing endothelial cell damage and in maintaining the anterior chamber during surgical manipulation, reports of elevated intraocular pressure, postoperatively, have been documented and it is recommended that this substance be removed from the anterior chamber prior to closing the corneal incision (MacRae et al., "The Effects of Sodium Hyaluronate, Chondroitin Sulfate and Methyl Cellulose on the Corneal Endothelium and Intraocular Pressure," supra). Lastly, hyaluronic acid does not adhere to intraocular lens surfaces or surgical instruments. By way of contrast, if one dips an intraocular lens into the viscoelastic collagen solution of this invention, the solution adheres to the surface of the intraocular lens, thereby providing an increased degree of endothelial protection.